Major Depressive Disorder (MDD)Phase 2NCT00768430

Optimization of IV Ketamine for Treatment Resistant Depression

A Phase 2 study testing Ketamine and Midazolam in people with Major Depressive Disorder (MDD) and Treatment Resistant Depression (TRD), run by Baylor College of Medicine at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 21 to 80 years
Conditions the study is for: Major Depressive Disorder (MDD), Treatment Resistant Depression (TRD)
What is being tested?: Ketamine and Midazolam
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 73 participants
Where: 2 sitesUnited States
Study dates: Nov 2008to Nov 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female patients, 21-80 years of age;
Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum beta-human growth hormone at screening and at pre-infusion;
Participants must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);
Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);
Participants have not responded to three or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);
Participant scores on the IDS-C30 must be greater than or equal to 32 at both Screening and within 24 hours prior to Visit 1a (Phase 1);

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Current major depressive episode is of at least 4 weeks duration.
Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document;
Each participant must be able to identify a family member, physician, or friend who will participate in the Treatment Contract.

Who cannot join

Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder
Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
Current diagnosis of Obsessive Compulsive Disorder or eating disorder (bulimia nervosa or anorexia nervosa);
Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
Patients judged clinically to be at serious and imminent suicidal or homicidal risk;

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Women who are either pregnant or nursing;
Serious, unstable medical illnesses including hepatic, renal, gastroenterologic (including gastroesophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
Patients with one or more seizures without a clear and resolved etiology;
Patients starting hormonal treatment (e.g., estrogen) in the last 3 months prior to Visit 1a;
Treatment with an irreversible MAOI or any other FDA approved Anti depressant medication within one week prior to Visit 1a (with the exception of a stable dose of non-benzodiazepines hypnotics i.e. zolpidem, eszopiclone, etc for at least 3 months);
Treatment with fluoxetine within 4 weeks prior to Visit 1a;
Evidence-based individual psychotherapy (e.g. CBT or IPT) and other non-pharmacological antidepressant treatments (e.g. light therapy) will not be permitted during the acute study period (7 day);
Previous recreational use of PCP or Ketamine.
Past intolerance or hypersensitivity to midazolam
Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) not controlled by diuretic or beta-blocker therapy alone or in combination.
Evidence of age-related cognitive decline or mild dementia suggested by a score of < 27 on the Mini-Mental State Examination (MMSE) at Screening

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Michael E. Dabakey VA Medical Center & Baylor College of Medicine
Houston, Texas, 77030
Mount Sinai School of Medicine
New York, New York, 10029

Other trials in United States

About this study

Official title: Optimization of Intravenous Ketamine for Treatment-Resistant Depression: A Randomized, Placebo-Controlled, Triple-masked, Clinical Trial

Existing treatments for major depressive disorder (MDD) generally take weeks to months to exert their maximal benefit. There is an urgent need to develop rapid-acting treatments for MDD. Ketamine, a high-affinity N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has been used as a standard intravenous (IV) anesthetic agent for many years in both pediatric and adult patients. Beyond its well-established role in anesthesia and pain management, there is emerging evidence that ketamine may have rapid antidepressant properties for patients with severe mood disorders.

In this study we are investigating whether ketamine can have an antidepressant effect compared to midazolam. Midazolam has similar anesthetic effects compared to ketamine but has not been shown to be an antidepressant, and is therefore acting as an active control in this study.

The study period can last up to 8 weeks, depending on your response to the study medication. There are two required overnight stays in our Research Commons as part of this study.

Conditions: Major Depressive Disorder (MDD), Treatment Resistant Depression (TRD)
Being tested: Ketamine, Midazolam
Medical subject headings: Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KetamineDrug
Also called Racemic ketamine hydrochloride
Single dose .5 mg/kg IV (in the vein) infused over 40 minutes
MidazolamDrug
single dose 0.045 mg/kg IV infused over 40 minutes

Study groups in NCT00768430
Study group	Role	What they receive
1	Experimental	Ketamine Receives: Drug: Ketamine
2	Active comparator	Midazolam Receives: Drug: Midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

MADRS
Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression.
Measured: 24 hours post-infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2008Nov 2012

First posted8 Oct 2008 (estimated)
Study startNov 2008
Primary completionSep 2012
Study completionNov 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
More trials run by Baylor College of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 73 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00768430
Sponsor's protocol ID: GCO 07-0114
Status last verified: Dec 2013
First submitted: 7 Oct 2008
Last updated: 31 Jan 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.
PubMed 16894061
Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.
PubMed 10686270
Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.
PubMed 25271445
Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392.
PubMed 23982301

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 31 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Optimization of Intravenous Ketamine for Treatment-Resistant Depression: A Randomized, Placebo-Controlled, Triple-masked, Clinical Trial
ClinicalTrials.gov ID: NCT00768430
Acronym / sponsor ID: GCO 07-0114
Conditions: Major Depressive Disorder (MDD), Treatment Resistant Depression (TRD)
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 73 participants (actual)
Lead sponsor: Baylor College of MedicineUniversity, hospital or other
Collaborators: Icahn School of Medicine at Mount Sinai
Study start: Nov 2008
Primary completion: Sep 2012 (actual)
Study completion: Nov 2012 (actual)
First posted: 8 Oct 2008 (estimated)
Results: Posted 31 Jan 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study period can last up to 8 weeks, depending on your response to the study medication. There are two required overnight stays in our Research Commons as part of this study.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: KetamineKetamine
2	Active comparator	Drug: MidazolamMidazolam

Who may qualify

Ages: 21 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Male or female patients, 21-80 years of age;
Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum beta-human growth hormone at screening and at pre-infusion;
Participants must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);
Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);
Participants have not responded to three or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);

Key exclusion criteria (18 listed)

Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder
Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
Current diagnosis of Obsessive Compulsive Disorder or eating disorder (bulimia nervosa or anorexia nervosa);
Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
KetamineAlso: Racemic ketamine hydrochlorideSingle dose .5 mg/kg IV (in the vein) infused over 40 minutes	Drug	1
Midazolamsingle dose 0.045 mg/kg IV infused over 40 minutes	Drug	2

Primary outcome

MADRS
Time frame: 24 hours post-infusion
Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression.

Results and safety

Results posted to the registry on 31 Jan 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ketamine	48	47
Midazolam	25	25

Primary outcome: MADRS

Time frame: 24 hours post-infusion. Mean (95% Confidence Interval). Unit: units on a scale

Measure	Ketamine n = 47	Midazolam n = 25
Value	14.77 (11.73 to 17.80)	22.72 (18.85 to 26.59)

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ketamine	2 of 47 (4.3%)	47 of 47 (100%)	Not reported
Midazolam	0 of 25 (0%)	25 of 25 (100%)	Not reported

Limitations and caveats (from the sponsor): Limitations of our trial include stringent enrollment criteria due to concerns about ketamine's psychoactive effects and abuse liability. A proportion of screened patients (17.2%) refused or were unable to tolerate psychotropic washout.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16894061Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.
Background: PubMed 10686270Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.
Derived from this study: PubMed 25271445Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.
Derived from this study: PubMed 23982301Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sanjay J. Mathew, MD principal investigator

Baylor College of Medicine

Dan V Iosifescu, MD,M.Sc. principal investigator

Icahn School of Medicine at Mount Sinai

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ketamine and Midazolam in people with Major Depressive Disorder (MDD) and Treatment Resistant Depression (TRD), run by Baylor College of Medicine at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MADRS (time frame: 24 hours post-infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00768430, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2014.